Genetic Variant NM_001394560.1:c.1678C>A (chrX-101883920-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394560.1(ZMAT1):c.1678C>A(p.Gln560Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,097,340 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000036 ( 0 hom. 1 hem. )

Consequence

ZMAT1
NM_001394560.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.10

Publications

2 publications found

Variant links:

Genes affected

ZMAT1 (HGNC:29377): (zinc finger matrin-type 1) This gene encodes a protein containing Cys2-His2 (C2H2)-type zinc fingers, which are similar to those found in the nuclear matrix protein matrin 3. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jan 2012]

ZMAT1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10357484).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394560.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMAT1	NM_001394560.1	MANE Select	c.1678C>A	p.Gln560Lys	missense	Exon 6 of 6	NP_001381489.1	Q5H9K5-3
ZMAT1	NM_001011657.4		c.1507C>A	p.Gln503Lys	missense	Exon 7 of 7	NP_001011657.2	Q5H9K5-1
ZMAT1	NM_001282400.2		c.994C>A	p.Gln332Lys	missense	Exon 10 of 10	NP_001269329.1	Q5H9K5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZMAT1	ENST00000651725.2	MANE Select	c.1678C>A	p.Gln560Lys	missense	Exon 6 of 6	ENSP00000498446.1	Q5H9K5-3
ZMAT1	ENST00000372782.4	TSL:1	c.1507C>A	p.Gln503Lys	missense	Exon 7 of 7	ENSP00000361868.3	Q5H9K5-1
ZMAT1	ENST00000878190.1		c.1747C>A	p.Gln583Lys	missense	Exon 7 of 7	ENSP00000548249.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000550

AC:

AN:

181865

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000123

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000365

AC:

AN:

1097340

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

363054

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26359

American (AMR)

AF:

0.00

AC:

AN:

35066

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19336

East Asian (EAS)

AF:

0.00

AC:

AN:

30182

South Asian (SAS)

AF:

0.00

AC:

AN:

54077

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40422

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4128

European-Non Finnish (NFE)

AF:

0.00000475

AC:

AN:

841730

Other (OTH)

AF:

0.00

AC:

AN:

46040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.93

FATHMM_MKL

Benign

0.57

M_CAP

Benign

0.033

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.0

PhyloP100

2.1

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.0

REVEL

Benign

0.025

Sift

Benign

0.052

Sift4G

Benign

0.33

Vest4

0.066

MutPred

0.22

Gain of ubiquitination at Q503 (P = 0.0042)

MVP

0.50

MPC

0.18

ClinPred

0.17

GERP RS

3.5

gMVP

0.35

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over